Peptide Information

General Information of This Peptide
Peptide ID
BTDP006322
Peptide Name
Alpha-conotoxin Vc1a
Symonym
ACV1; Vc1.1
Species
Conus victoriae (Queen Victoria cone)
Uniprot Name
CA1A_CONVC
Alphafold ID
P69747
3D Structure
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2D Sequence
3D Structure
Source
RSCB PDB: 2H8S
Sequence
MGMRMMFTVFLLVVLATTVVSSTSGRREFRGRNAAAKASDLVSLTDKKRGCCSDPRCNYD
HPEICG
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Sequence Length
66
Mass (Da)
7258
Signal Sequence
MGMRMMFTVFLLVVLATTVVS
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Sequence Removed Signal Peptide
STSGRREFRGRNAAAKASDLVSLTDKKRGCCSDPRCNYDHPEICG
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Disulfide Bond
51-57;52-65
PDB ID
2H8S , 2MFX , 2MFY , 2MG6 , 2N07 , 4TTL , 6CGX , 7KNN
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Kingdom: Metazoa
Phylum: Mollusca
Class: Gastropoda
Order: Neogastropoda
Family: Conidae
Genus: Conus
Species: Conus victoriae
Full List of Activity Data of This Peptide Toxin
                        Target Name Activity Data Type Activity Data Concentration Note Reference
 Target Info    HVA calcium channel IC50
0.3 nM
 .
CVc1.1
 [1- 17]
 Target Info    GABBR1 and/or GABBR2 IC50
1.7 nM
 .
Vc1.1
 [1- 17]
 Target Info    HVA calcium channel IC50
3.3 nM
 .
CVc1.1[D11A; E14A]
 [1- 17]
 Target Info    nAChR alpha-9-alpha-10 IC50
19 - 109 nM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-9-alpha-10 IC50
62.9 nM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-6/alpha-3-beta-2-beta-3 IC50
140 nM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-9-alpha-10 IC50
766 nM
 .
CVc1.1
 [1- 17]
 Target Info    nAChR alpha-6/alpha-3-beta-4 IC50
980 nM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-1-beta-1-gamma-delta IC50
>30 μM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-3-alpha-5-beta-4 IC50
>30 μM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-4-beta-2 IC50
>30 μM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-4-beta-4 IC50
>30 μM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-3-beta-4 IC50
4.2 μM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-3-beta-2 IC50
5.5 - 7.3 μM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-7 IC50
7.1 μM
 .
Vc1.1
 [1- 17]
 Target Info    nAChR alpha-3-alpha-5-beta-2 IC50
7.2 μM
 .
Vc1.1
 [1- 17]
References
Ref 1 A novel alpha-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo. Biochemistry. 2003 Jun 10;42(22):6904-11. doi: 10.1021/bi034043e.
Ref 2 Determining sequences and post-translational modifications of novel conotoxins in Conus victoriae using cDNA sequencing and mass spectrometry. J Mass Spectrom. 2004 May;39(5):548-57. doi: 10.1002/jms.624.
Ref 3 A conus peptide blocks nicotinic receptors of unmyelinated axons in human nerves. Neuroreport. 2005 Apr 4;16(5):479-83. doi: 10.1097/00001756-200504040-00012.
Ref 4 Molecular mechanism for analgesia involving specific antagonism of alpha9alpha10 nicotinic acetylcholine receptors. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17880-4. doi: 10.1073/pnas.0608715103. Epub 2006 Nov 13.
Ref 5 Are alpha9alpha10 nicotinic acetylcholine receptors a pain target for alpha-conotoxins?. Mol Pharmacol. 2007 Dec;72(6):1406-10. doi: 10.1124/mol.107.040568. Epub 2007 Sep 5.
Ref 6 Analgesic alpha-conotoxins Vc1.1 and Rg1A inhibit N-type calcium channels in rat sensory neurons via GABAB receptor activation. J Neurosci. 2008 Oct 22;28(43):10943-51. doi: 10.1523/JNEUROSCI.3594-08.2008.
Ref 7 Scanning mutagenesis of alpha-conotoxin Vc1.1 reveals residues crucial for activity at the alpha9alpha10 nicotinic acetylcholine receptor. J Biol Chem. 2009 Jul 24;284(30):20275-84. doi: 10.1074/jbc.M109.015339. Epub 2009 May 15.
Ref 8 Determination of the -conotoxin Vc1.1 binding site on the 910 nicotinic acetylcholine receptor. J Med Chem. 2013 May 9;56(9):3557-67. doi: 10.1021/jm400041h. Epub 2013 Apr 29.
Ref 9 Structure-Activity Studies of Cysteine-Rich -Conotoxins that Inhibit High-Voltage-Activated Calcium Channels via GABA(B) Receptor Activation Reveal a Minimal Functional Motif. Angew Chem Int Ed Engl. 2016 Apr 4;55(15):4692-6. doi: 10.1002/anie.201600297. Epub 2016 Mar 7.
Ref 10 Cyclic analogues of -conotoxin Vc1.1 inhibit colonic nociceptors and provide analgesia in a mouse model of chronic abdominal pain. Br J Pharmacol. 2018 Jun;175(12):2384-2398. doi: 10.1111/bph.14115. Epub 2018 Feb 13.
Ref 11 Dimerization of -Conotoxins as a Strategy to Enhance the Inhibition of the Human 7 and 910 Nicotinic Acetylcholine Receptors. J Med Chem. 2020 Mar 26;63(6):2974-2985. doi: 10.1021/acs.jmedchem.9b01536. Epub 2020 Mar 17.
Ref 12 The synthesis, structural characterization, and receptor specificity of the alpha-conotoxin Vc1.1. J Biol Chem. 2006 Aug 11;281(32):23254-63. doi: 10.1074/jbc.M604550200. Epub 2006 Jun 5.
Ref 13 The engineering of an orally active conotoxin for the treatment of neuropathic pain. Angew Chem Int Ed Engl. 2010 Sep 3;49(37):6545-8. doi: 10.1002/anie.201000620.
Ref 14 Dicarba -conotoxin Vc1.1 analogues with differential selectivity for nicotinic acetylcholine and GABAB receptors. ACS Chem Biol. 2013 Aug 16;8(8):1815-21. doi: 10.1021/cb4002393. Epub 2013 Jun 17.
Ref 15 Racemic and quasi-racemic X-ray structures of cyclic disulfide-rich peptide drug scaffolds. Angew Chem Int Ed Engl. 2014 Oct 13;53(42):11236-41. doi: 10.1002/anie.201406563. Epub 2014 Aug 28.
Ref 16 Less is More: Design of a Highly Stable Disulfide-Deleted Mutant of Analgesic Cyclic -Conotoxin Vc1.1. Sci Rep. 2015 Aug 20;5:13264. doi: 10.1038/srep13264.
Ref 17 Structure-Activity Studies Reveal the Molecular Basis for GABA(B)-Receptor Mediated Inhibition of High Voltage-Activated Calcium Channels by -Conotoxin Vc1.1. ACS Chem Biol. 2018 Jun 15;13(6):1577-1587. doi: 10.1021/acschembio.8b00190. Epub 2018 May 25.
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